Project Summary: Dr. Meng Wu is Director of the University of Iowa High Throughput Screening Facility (UIHTS), a shared resource of the NCI-designated Holden Comprehensive Cancer Center (HCCC). He is mentored by Dr. George Weiner, Director of the HCCC and PI of Cancer Center Support Grant (CCSG) 5 P30 CA086862-18. Dr. Wu has extensive expertise in high throughput screening, assay development and adaption, fluorescent and label-free detection, the discovery of small-molecule probes and drug leads, high content imaging, and high throughput data analysis; this is evident from his 230 BioAssays in PubChem and 41 publications in PubMed). The UIHTS was established in 2012 by university sponsors including the HCCC. Dr. Wu is the inaugural director of the UIHTS and has overseen the establishment and maintenance of every aspect of the facility, including acquisition of both high throughput and high content imaging equipment, construction of chemical and biological libraries, and establishment of biochemical as well as cell-based standard operating procedures (SOPs). Dr. Wu also streamlined the workflow, from project recruitment, assay development, compound management, high throughput/content screening, data and image analysis, hit-picking and dose-response validation/confirmation, to preliminary datasets for external grant application and final datasets for publication. This effort resulted in integration of the UIHTS into the HCCC as a core facility during its renewal in 2016. Dr. Wu's scientific and administrative leadership of the UIHTS has provided HCCC investigators access to new scientific approaches by a high-throughput platform for integrating robotics, high throughput and high content detection systems, chemical/biologics libraries (small-molecule drugs, arrayed CRISPR gRNAs, and cell lines), data management, and technical expertise. In 2018 alone, the UIHTS core supported 15 NCI-supported projects, among 27 peer reviewed (external funded) cancer research projects, contributing to assay development and high throughput screening. In this NCI R50 proposal, we request salary support for Dr. Wu under Dr. Weiner's mentorship, to support him in the following activities: 1) continued high throughput screening in collaboration with the basic and translational cancer research community, for the discovery of novel probes and therapeutics for cancer patients; 2) development of novel high throughput-compatible assays/technologies (e.g., involving the use of 3D- spheroids, patient-derived organoids, co-culture cell systems) to enable more direct patient-relevant screening approaches; 3) facilitation of systematic, un-biased optimization of synergetic effects of FDA-approved drugs and immune-oncological therapeutics for novel clinical trials; and 4) exploration of the use of patient-derived cells and spheroids in evidence-based precision medicine. Support from the NCI in the form of a Research Specialist Award, together with mentorship and support from the HCCC, will enable Dr. Wu to make a crucial contribution to the overall goals of the HCCC.